Recurrent/metastatic relapse after definitive treatment for HNSCC: timing, patterns, and survival

Background Timing and outcomes of recurrence after definitive therapy for HNSCC are incompletely understood. Methods This study included patients in a nationwide EHR-derived de-identified database who received systemic therapy for R/M HNSCC. Time from definitive treatment to R/M systemic therapy initiation (TTRM), and overall survival (OS) from R/M systemic therapy initiation, were estimated and compared between patients stratified by cancer site and prior definitive treatment modality. Results Of 7657 patients receiving R/M therapy, the median age was 65 (IQR 58-72), 77% male, 74% white, 79% with smoking history, and 79% ECOG PS 0-1. 1684 (22%) patients had no recorded prior definitive therapy ( de novo metastatic); of the remaining 5973 patients, most common definitive treatment types were radiation alone (RT only; 43%), followed by surgery plus radiation (Surg + RT; 21%), surgery alone (Surg only; 16%), chemoradiation (CRT; 14%), and surgery plus chemoradiation (Surg + CRT; 6%). Patients treated with high-risk treatment types (Surg + CRT, CRT) had higher disease stage at presentation, shorter TTRM (median 6–7 vs 17–19 months), and shorter OS from R/M treatment to death (median 8 vs 12 months) compared to patients in low-risk treatment groups (RT only, Surg + RT, Surg only). Patients with HPV+ oropharynx cancer had numerically longer TTRM (median 17 vs 13 months, p = 0.4309) and significantly longer OS (median 18 vs 10 months, p < 0.001) than HPV- cancers. Conclusions Patients with locoregionally advanced HNSCC treated with CRT and surgery plus CRT represent a high-risk cohort with rapid R/M disease and poor survival, who need improved therapeutic options.